This invention relates to methods, compositions and kits for detecting the presence and/or amounts of entactogens in samples suspected of containing the same. In particular, the invention relates to haptens, immunogens and assays for 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxy-methamphetamine (MDMA), 3,4-methylenedioxy-ethylamphetamine (MDEA) and 4-hydroxy-3-methoxy-methamphetamine (HMMA).
The clinical diagnostic field has seen a broad expansion in recent years, both as to the variety of materials of interest that may be readily and accurately determined, as well as the methods for the determination. Over the last decade, testing for drugs of abuse has become commonplace. This testing is not only for the monitoring of criminal offenders and drug addicts, but employers also use it for the screening of workers. In recent years, immunoassay based on the reaction of an antibody with an antigen has been extensively investigated for this purpose. Immunoassay may be roughly classified into radioimmunoassay, using a radioactive isotope, enzyme-immunoassay (EIA) using an enzyme and luminescence assays, using fluorescent labels, e.g., fluorescence polarization, and chemiluminescent labels.
Amphetamine and methamphetamine stimulate the central nervous system and have been used medicinally to treat hypotension, narcolepsy and obesity. Because of their stimulating effects, the drugs and derivatives have been abused.
The designer drugs, methylenedioxyamphetamine (MDA), 1-3′,4′-methylenedioxyphenyl)-2-propanamine, “Love Pills”, methylenedioxy-methamphetamine (MDMA), “Adam”, “Ecstasy” and methylenedioxyethylamphetamine (MDEA), “Eve” are entactogens, producing feeling of euphoria and friendliness. These drugs are currently popular and called “rave drugs”. It has been demonstrated by several experimental studies on rats and human that these drugs are risky to human. In fact, toxicity and deaths associated with MDMA has been reported. Recent reviews have also reported the hepatotoxicity, neurotoxicity, psychopathology and the abuse potential of these drugs. The common use of these drugs has been widespread in the world and appeared recently as the most popular drug of abuse in certain countries.
Although there is a need for the detection of MDMA, MDA and its metabolites such as 4-hydroxy-3-methoxymethamphetamine (HMMA) and so forth, the literature discloses GC-MS, HPLC detection methods, which are expensive and time consuming. It appears that researchers have tried to use existing amphetamine/methamphetamine immunoassay technology for the detection of MDMA and MDA due to their cross-reactivity. The hope was that the antibody recognizing amphetamine and methamphetamine would also be useful for assays for MDMA, MDA or its metabolites. For instance, three commercial amphetamine/methamphetamine assays, namely, EMIT®, FPIA and RIA, have been investigated for the detection of MDA, MDMA and MDEA. (Ruangyuttikarn, et al., “Comparison of three commercial amphetamine immunoassay for detection of methamphetamine, methylenedioxyamphetamine, methylenedioxy-methamphetamine and methylenedioxyethylamphetamine” J. Anal. Toxicol. 1988, 12, 229; Kunsman, et al., “Application of the Syva Emit and Abbott TDX amphetamine Immunoassays to the detection of 3,4-Methylenedioxy-methamphetamine (MDMA) and 3,4-Methylenedioxyethamphetamine (MDEA) in Urine” J. Anal. Toxicol. 1990, 14, 149; Cody, J. T. “Detection of D,L-amphetamine, D,L-methamphetamine, and illicit amphetamine analogs using diagnostic products corporation's amphetamine and methamphetamine radioimmunoassay” J. Anal. Toxicol. 1990, 14, 321; Ensslin, et al., “Toxicological detection of the designer drug 3,4-methylenedioxyethylamphetamine (MDE, ‘Eve’) and its metabolites in urine by gas chromatography spectrometry and fluorescence polarization immunoassay” J. Chromatogr. 1996, B683, 189.
However, according to the published literature, the above approaches have achieved little, if any, success. This result is not unexpected due to the very different chemical structures between methamphetamine and MDMA analogs. That is, MDMA and MDA have an extra (methylenedioxy) five-member ring in comparison to methamphetamine and amphetamine, respectively.
There is, therefore, a need for assays for the detection of the aforementioned designer drugs and, in some instances, their major metabolites. The assays should be able to detect the designer drugs in order to monitor and treat patients addicted to these drugs.